tbuckley/cabot-search huggingface dataset:
Phase II, Open-Label Study of Ciltacabtagene Autoleucel, an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor–T-Cell Therapy, in Chinese Patients With Relapsed/Refractory Multiple Myeloma (CARTIFAN-1)
Authors: Jian-Qing Mi, Wanhong Zhao, Hongmei Jing, Weijun Fu, Jianda Hu, Lijuan Chen, Yiwen Zhang, Dan Yao, Diana Chen, Jordan M. Schecter, Fan Yang, Xiaochen Tian, Huabin Sun, Sen Hong Zhuang, Jimmy Ren, Xiaohu Fan, Jie Jin, Ting Niu, Sai-Juan Chen
Journal: Journal of Clinical Oncology (2022)

CARTIFAN-1 aimed to evaluate the efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeting chimeric antigen receptor T-cell therapy, in Chinese patients with relapsed/refractory multiple myeloma (RRMM).This pivotal phase II, open-label study (ClinicalTrials.gov identifier: NCT03758417), conducted across eight sites in China, enrolled adult patients with RRMM who had received ≥ 3 lines of prior therapy, including a proteasome inhibitor and immunomodulatory drug. Patients received a single infusion of cilta-cel (target dose 0.75 × 106 chimeric antigen receptor-positive viable T cells/kg). The primary end point was overall response rate. Secondary end points included progression-free survival (PFS), overall survival (OS), and incidence and severity of adverse events (AEs).As of the clinical cutoff of July 19, 2021, 48 patients received a cilta-cel infusion. At an 18-month median follow-up, the overall response rate was 89.6% (95% CI, 77.3 to 96.5), with a median time to first response of approximately 1 month; 77.1% of patients (95% CI, 62.7 to 88.0) achieved complete response or better. Medians for duration of response, PFS, and OS were not reached. The 18-month PFS and OS rates were 66.8% (95% CI, 49.4 to 79.4) and 78.7% (95% CI, 64.0 to 88.0), respectively. Hematologic AEs were common, including anemia (100%), neutropenia (97.9%), lymphopenia (95.8%), and thrombocytopenia (87.5%). Cytokine release syndrome occurred in 97.9% of patients (35.4% grade 3/4); the median time to onset was 7 days, and the median duration was 5 days. Infections occurred in 85.4% of patients (37.5% grade 3/4). Ten deaths occurred after cilta-cel infusion, eight of which were due to treatment-related AEs.These data demonstrate a favorable risk-benefit profile for a single infusion of cilta-cel, resulting in early, deep, and durable responses in heavily pretreated patients with RRMM in China.
The end of the rainbow? Preserving a symbol of LGBTQ+ allyship in the NHS
Authors: Nicholas Phillips
Journal: BMJ (2022)

a symbol of LGBTQ+ allyship in the NHS Efforts to promote a safe and positive healthcare environment for the LGBTQ+ community should be undertaken with renewed focus in the wake of the pandemic, says Nicholas Phillips Nicholas Phillips fifth year intercalating medical studentThe covid-19 pandemic saw the image of the NHS logo next to a rainbow become a national symbol of appreciation for patient facing workers.Rainbows and messages of thanks were scrawled on the windows of homes, unfurled on flags and signs outside shops and public buildings, and emblazoned on badges and tote bags.As the use of this image as a token of thanks to NHS staff proliferated, however, the message it initially represented in the NHS-as a symbol of LGBTQ+ allyship-started to blur.
Injectable bone marrow microniches by co-culture of HSPCs with MSCs in 3D microscaffolds promote hematopoietic reconstitution from acute lethal radiation
Authors: Haiwei Liang, Yanxiao Ao, Wenjing Li, Kaini Liang, Baixue Tang, Junyang Li, Jianwei Wang, Xiaoyu Zhu, Yanan Du
Journal: Bioactive Materials (2022)

Hematopoietic syndrome of acute radiation syndrome (h-ARS) is an acute illness resulted from the damage of bone marrow (BM) microenvironment after exposure to radiation. Currently, the clinical management of h-ARS is limited to medication-assisted treatment, while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure. Our study aimed to assemble biomimetic three-dimensional (3D) BM microniches by co-culture of hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stem cells (MSCs) in porous, injectable and viscoelastic microscaffolds in vitro. The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS. We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84 μm in pore diameter and 11.2 kPa in Young's modulus compared with 2D co-culture system. Besides, the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS, which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs. Furthermore, the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs, while the Jagged1 expression of the co-cultured MSCs was upregulated, indicating the significance of Notch signaling pathway in maintenance of HSPCs. Collectively, our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs, promote hematopoiesis regeneration and alleviate post-radiation injury, which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.
Primary tumor–derived systemic nANGPTL4 inhibits metastasis
Authors: Corinne Hübers, Ashik Ahmed Abdul Pari, Denise Grieshober, Martin Petkov, Alexander Schmidt, Tatjana Messmer, Christian Moritz Heyer, Sebastian Schölch, Stephanie S. Kapel, Nicolas Gengenbacher, Mahak Singhal, Benjamin Schieb, Claudine Fricke, Rainer Will, Kim Remans, Jochen Sven Utikal, Christoph Reissfelder, Matthias Schlesner, Kairbaan M. Hodivala-Dilke, Sander Kersten, Sergij Goerdt, Hellmut G. Augustin, Moritz Felcht
Journal: The Journal of Experimental Medicine (2022)

Primary tumors and distant site metastases form a bidirectionally communicating system. Yet, the molecular mechanisms of this crosstalk are poorly understood. Here, we identified the proteolytically cleaved fragments of angiopoietin-like 4 (ANGPTL4) as contextually active protumorigenic and antitumorigenic contributors in this communication ecosystem. Preclinical studies in multiple tumor models revealed that the C-terminal fragment (cANGPTL4) promoted tumor growth and metastasis. In contrast, the N-terminal fragment of ANGPTL4 (nANGPTL4) inhibited metastasis and enhanced overall survival in a postsurgical metastasis model by inhibiting WNT signaling and reducing vascularity at the metastatic site. Tracing ANGPTL4 and its fragments in tumor patients detected full-length ANGPTL4 primarily in tumor tissues, whereas nANGPTL4 predominated in systemic circulation and correlated inversely with disease progression. The study highlights the spatial context of the proteolytic cleavage-dependent pro- and antitumorigenic functions of ANGPTL4 and identifies and validates nANGPTL4 as a novel biomarker of tumor progression and antimetastatic therapeutic agent.
Association of the Expiration of Child Tax Credit Advance Payments With Food Insufficiency in US Households
Authors: Allison Bovell-Ammon, Nicole C. McCann, Martha Mulugeta, Stephanie Ettinger de Cuba, Julia Raifman, Paul Shafer
Journal: JAMA Network Open (2022)

Advance Child Tax Credit (CTC) monthly payments administered to more than 35 million households with children in the US between July and December 2021 were associated with a substantial decrease in food insufficiency. These monthly payments expired in January 2022 after Congress failed to extend the policy, and the subsequent impact on food insufficiency is currently unknown.To assess whether the expiration of monthly CTC payments in January 2022 was associated with changes in food insufficiency in US households with children.This study used repeated cross-sectional, nationally representative data from multiple waves of the Household Pulse Survey, conducted by the US Census Bureau. Online data collection occurred from July 21, 2021, to July 11, 2022, and data analysis was performed in July 2022.The first missed advance CTC payment on January 15, 2022.The main outcome was unadjusted prevalence of household food insufficiency. Event study specification was used to estimate the association between the expiration of the CTC payments and household food insufficiency with the exposure of being in a household with children present.The sample (592 044 respondents, representing households with and without children, for a weighted population size of 123 350 770 individuals) was majority female (362 286 individuals [51.3%]) and non-Hispanic White (425 497 individuals [62.2%]), and a plurality of respondents (248 828 [48.3%]) were aged 25 to 44 years at the time of the survey. During the survey wave just before CTC expiration (reference wave, December 29, 2021, to January 10, 2022), unadjusted household food insufficiency was 12.7% among households with children. In late January and early February 2022, following the first missed CTC monthly payment, 13.6% of households with children reported food insufficiency, increasing to 16.0% by late June and early July 2022. The event study specification estimated a 3.2 percentage point increase (95% CI, 1.4-5.0 percentage points; P < .001) in food insufficiency by the most recent wave available after the first missed CTC payment (June 29 to July 11, 2022) among households with children compared with the reference wave, a 25% increase.The findings of this study suggest that there was an increase in food insufficiency among households with children after they stopped receiving monthly CTC payments. Given the well-documented associations between inability to afford food and poor health outcomes across the life span, Congress should consider swift action to reinstate this policy.
Effect of a Novel Brief Motivational Intervention for Alcohol-Intoxicated Young Adults in the Emergency Department
Authors: Jacques Gaume, Nicolas Bertholet, Jim McCambridge, Molly Magill, Angéline Adam, Olivier Hugli, Jean-Bernard Daeppen
Journal: JAMA Network Open (2022)

Heavy drinking among young adults is a major public health concern. Brief motivational interventions in the emergency department have shown promising but inconsistent results. To test whether young adults receiving a newly developed brief motivational intervention reduce their number of heavy drinking days and alcohol-related problems over 1 year compared with participants receiving brief advice. This randomized clinical trial was conducted at an emergency department of a tertiary care university hospital in Lausanne, Switzerland. Recruitment ran from December 2016 to August 2019. Follow-up was conducted after 1, 3, 6, and 12 months. All adults aged 18 to 35 years presenting for any cause and presenting with alcohol intoxication were eligible (N = 2108); 1764 were excluded or refused participation. Follow-up rate was 79% at 12 months and 89% of participants provided follow-up data at least once and were included in the primary analyses. Statistical analysis was performed from September 2020 to January 2021. The novel intervention was based on motivational interviewing and comprised in-person discussion in the emergency department and up to 3 booster telephone calls. The control group received brief advice. Primary outcomes were the number of heavy drinking days (at least 60 g of ethanol) over the previous month and the total score on the Short Inventory of Problems (0-45, higher scores indicating more problems) over the previous 3 months. Hypotheses tested were formulated before data collection. There were 344 young adults included (median [IQR] age: 23 [20-28] years; 84 women [24.4%]). Among the 306 participants providing at least 1 follow-up point, a statistically significant time × group interaction was observed (β = -0.03; 95% CI, -0.05 to 0.00; P = .02), and simple slopes indicated an increase of heavy drinking days over time in the control (β = 0.04; 95% CI, 0.02 to 0.05; P < .001) but not in the intervention group (β = 0.01; 95% CI, -0.01 to 0.03; P = .24). There was no effect on the Short Inventory of Problems score (β = -0.01; 95% CI, -0.03 to 0.02; P = .71). This randomized clinical trial found that a brief motivational intervention implemented in the emergency department provided beneficial effects on heavy drinking, which accounts for a substantial portion of mortality and disease burden among young adults. ISRCTN registry: 13832949.
Preparing Europe for future health threats and crises ─ the European Medicines Agency; ensuring safe and effective medicines and medical devices
Authors: Emer Cooke
Journal: Eurosurveillance (2022)

Preview this article: Preparing Europe for future health threats and crises ─ the European Medicines Agency; ensuring safe and effective medicines and medical devices, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/27/42/eurosurv-27-42-1-1.gif
External quality assessment of SARS-CoV-2 serology in European expert laboratories, April 2021
Authors: Ramona Mögling, Francesca Colavita, Johan Reimerink, Angeliki Melidou, Katrin Leitmeyer, Maria Keramarou, Daniele Lapa, Massimo Francalancia, Jean-Luc Murk, Ann Vossen, Fabrizio Carletti, Boris Hogema, Adam Meijer, Liesbet Deprez, Antonino di Caro, Concetta Castilletti, Chantal BEM Reusken
Journal: Eurosurveillance (2022)

BackgroundCountries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS-CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration.AimThe aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment (EQA) based on proficiency testing.MethodsThe EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS-CoV-2 serological standards were sent to 56 laboratories in 30 countries.ResultsThe overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS-CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards.ConclusionOur EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti-SARS-CoV-2 antibodies are available.
High monkeypox vaccine acceptance among male users of smartphone-based online gay-dating apps in Europe, 30 July to 12 August 2022
Authors: Juliana Reyes-Urueña, Angelo D'Ambrosio, Roberto Croci, Benjamin Bluemel, Orlando Cenciarelli, Anastasia Pharris, Nicole Dukers-Muijrers, Will Nutland, Steph Niaupari, Jawad Badran, Gianfranco Spiteri, Teymur Noori
Journal: Eurosurveillance (2022)

We assess monkeypox vaccination acceptance among male adults in the European Region. We conducted an online survey through two dating apps targeting men who have sex with men, from 30 July to 12 August 2022. We developed Bayesian hierarchical logistic regression models to investigate monkeypox vaccination acceptance. Overall crude vaccination acceptance was 82% and higher in north-western compared to south-eastern European regions. Acceptance strongly rose with perception of increased disease severity and transmission risk, and in individuals linked to healthcare.
Mediterranean spotted fever-like illness caused by Rickettsia sibirica mongolitimonae, North Macedonia, June 2022
Authors: Dejan Jakimovski, Sofija Mateska, Verica Simin, Ivana Bogdan, Dragana Mijatović, Agustín Estrada-Peña, Lourdes Mateos-Hernández, Angélique Foucault-Simonin, Sara Moutailler, Alejandro Cabezas-Cruz, Pavle Banović
Journal: Eurosurveillance (2022)

Mediterranean spotted fever-like illness (MSF-like illness) is a tick-borne disease caused by Rickettsia sibirica mongolitimonae first reported in France more than 25 years ago. Until today, more than 50 cases of MSF-like illness have been reported in different regions of Europe and Africa, highlighting variable clinical manifestation. Here we report a case of MSF-like illness following a bite from a Hyalomma tick in the Skopje region of North Macedonia.
Variation in Human Papillomavirus Vaccination Effectiveness in the US by Age at Vaccination
Authors: Didem Egemen, Hormuzd A. Katki, Anil K. Chaturvedi, Rebecca Landy, Li C. Cheung
Journal: JAMA Network Open (2022)

This survey study assesses the status and timing of HPV vaccination as self-reported by female participants in the National Health and Nutrition Examination Survey from 2011 to 2018.
Guide to optimizing care for Muslim patients with knee osteoarthritis
Authors: Mahfujul Z. Haque, Usman Virk, Ameen Suhrawardy, Karl C. Roberts, Marina N. Magrey
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
EV packing allows meningioma tracking in blood
Authors: Susan C Short
Journal: Neuro-Oncology (2022)

Liquid biopsies which detect tumor-derived material in blood or other body fluids have enormous potential in cancer diagnosis and monitoring and are already in clinical use in many solid tumors. The minimally invasive nature of sampling enables multiple-time point tracking to monitor response and inform management decisions, for example, by assaying circulating tumor DNA (ctDNA) in the setting of de novo or treatment-induced mutation.1 Blood based sampling has also been implemented for personalized medicine in early phase clinical studies and is increasingly being explored as a screening approach. In brain tumors the approaches that have been used in other malignancies, relying on detection of circulating tumor cells or tumor DNA are more challenging since shedding of relevant material into blood is much less common, presumably due to restricted passage across the tumor/blood barrier. Studies examining the use of circulating tumor cells or ctDNA in blood in glioma patients have confirmed that sensitivity is low.2 Sampling CSF improves sensitivity and has promising utility in pediatric tumors, but is more invasive and unlikely to be appropriate in the majority of patients in most settings.3 These challenges have forced the neuro oncology research community to investigate alternative assays to improve sensitivity for detection of tumor genomic material as well as to explore completely different approaches, which have opened a fascinating window into cellular cargo trafficking in cancer patients. One of these is the identification of endosome derived extracellular vesicles (EVs) as a source of tumor-derived material that can be isolated from blood. These EVs include exosomes, microvesicles, and oncosomes that carry cargoes including DNA, RNA, lipids, and proteins. Carriage within EV protects ctDNA and RNA from degradation, thereby providing an advantage in terms of half-life of tumor genomic material in blood. Previously published data have confirmed raised levels compared to healthy controls and suggested utility as circulating biomarkers in range of solid tumours.4
ONCOS-102: A Step Forward or Sideways?
Authors: Shoshana T. Levi, Genevieve M. Boland
Journal: Clinical Cancer Research (2022)

Summary Treatment of anti–PD-1 refractory melanoma remains a challenge. Intratumoral injection of ONCOS-102, a chimeric oncolytic adenovirus expressing GMCSF, into anti–PD-1–resistant melanoma with administration of pembrolizumab was safe and effective. Response to therapy was associated with increased lymphocyte infiltration and expression of cytotoxicity and costimulatory genes. See related article by Shoushtari et al., p. 100
Increase in Food Insufficiency Among Households With Children After Expiration of Monthly Child Benefits
Authors: Nicole L. Kovski
Journal: JAMA Network Open (2022)

Allison Bovell-Ammon, MDiv; Nicole C. McCann, BA; Martha Mulugeta, MPH; Stephanie Ettinger de Cuba, PhD, MPH; Julia Raifman, ScD; Paul Shafer, PhD
COVID-19 Has Exacerbated Inequities That Hamper Physician Workforce Diversification
Authors: James N. Woodruff, William A. McDade, Sunny Nakae, Monica B. Vela
Journal: JAMA Network Open (2022)

Jasmine Weiss, MD, MHS; Louisa Holaday, MD, MHS; Danya Keene, PhD; Ngozi D. Akingbesote, BS; Lilanthi Balasuriya, MD; Mona Sharifi, MD, MPH; Darin Latimore, MD; Inginia Genao, MD
Public health measures during the COVID-19 pandemic through the lens of community organisations and networks in the Netherlands (2020–2021): five lessons for pandemic decision-making
Authors: Carla Kolner, Wieke van der Borg, Jet Sanders, Jolanda Keijsers, Maysa Joosten, Marijn de Bruin
Journal: Eurosurveillance (2022)

BackgroundDuring the coronavirus disease (COVID-19) pandemic, key persons who were formally or informally active in community organisations and networks, such as sports clubs or cultural, educational, day care and healthcare facilities, occupied a key position between governments and citizens. However, their experiences, the dilemmas they faced and the solutions they generated when implementing COVID-19 measures in their respective settings are understudied.AimWe aimed to understand how key persons in different community organisations and networks experienced and responded to the COVID-19 measures in the Netherlands.MethodsBetween October 2020 and December 2021, the Corona Behavioural Unit at the Dutch national public health institute, conducted qualitative research based on narratives derived from 65 in-depth interviews with 95 key persons from 32 organisations and networks in eight different sectors.ResultsFirstly, key persons enhanced adherence and supported the resilience and well-being of people involved in their settings. Secondly, adherence was negatively affected where COVID-19 measures conflicted with important organisational goals and values. Thirdly, small changes and ambiguities in COVID-19 policy had substantial consequences, depending on the context. Fourthly, problem-solving was achieved through trial-and-error, peer support, co-creation and transparent communication. Lastly, the COVID-19 pandemic and measures highlighted inequalities in access to resources.ConclusionPandemic preparedness requires organisational and community preparedness and a multidisciplinary public health approach. Structural engagement of governments with key persons in community organisations and networks is key to enhance public trust and adherence to pandemic measures and contributes to health equity and the well-being of the people involved.